The purpose of this grant is to bring a variety of scientific disciplines to bear on a number of specific drug abuse problems. We propose to carry out major projects in the areas of chemical receptor probes, narcotic agonists and antagonists, the dependence potential of the cannabinoids, effects of opioid and other drugs of dependence on the immune system and methodology development. In the area of chemical receptor probes, we plan to synthesize specific compounds for studies of the postulated opioid "cough" , PCP, sigma agonist and nicotine receptors. In the narcotic area, we plan to extend our studies toward the elucidation of the various opioid "cough" and sigma agonist receptors. We will continue to pharmacologically characterize opiate agonists and antagonists from our synthetic and drug abuse programs. Our studies with the cannabinoids will concentrate on assessing the dependence potential of delta-9-THC, the active principle of marijuana. We will then extend these findings to other cannabinoids as well as other classes of hallucinogens. We plan to continue our efforts to develop methods for better evaluating the reinforcing efficacy of drugs of abuse. That is, why do some drugs act as more powerful reinforcers of behavior than others and what can we do to alter this? We will complete our studies of cocaine and proceed to other classes of abused drugs. We will initiate a major study on the effects of drugs of abuse and the dependence cycle on the immune system. We will begin with the opioids and extend our studies to other classes of dependence producing substances. The increasing incidence of AIDS in the intravenous drug abusing population calls for detailed studies on the effects of drugs of abuse and the cycle of dependence and withdrawal on the immune system.